Frequency Therapeutics — Hearing Loss Regeneration

[Keith Handy]

This came up in my YouTube subscriptions today. It has optional captioning if you don't want audio. As far as I can tell, it's pretty accurate. This is what a more mainstream audience would probably be viewing to keep up with info on hearing loss developments; feel free to point out any inaccuracies you may spot. I didn't notice any.

 

[Cernuto]

I answered every one, there was only one word on the whole list that I thought could have been two different words and said them both... not sure if that counted as a missed word. I don't recall being told I had to guess, either, but doesn't every short word at least sound like something when you haven't heard it clearly? The mind fills in blanks immediately. "S'cuse me while I kiss this guy," etc. Saying "I don't know" for a one syllable word seems odd.

Would you say it's a subjective test?

Of course the placebo effect is real. I just don't see it doing something that has historically not been possible (doubling word scores in chronic hearing loss).

The placebo effect is limited to possible things. E.g., Paraplegic people can't walk due to placebo.

Some studies show actual physical changes due to the placebo effect. Combine that with the fact that a hearing test can be a subjective thing:

Audiologist: "Don't raise your hand if you can't hear this tone I'm playing."
Me: "I always hear a tone."
Audiologist: "Don't get smart!"

 

[Guywithapug]

This came up in my YouTube subscriptions today. It has optional captioning if you don't want audio. As far as I can tell, it's pretty accurate. This is what a more mainstream audience would probably be viewing to keep up with info on hearing loss developments; feel free to point out any inaccuracies you may spot. I didn't notice any.

In this video, I'm going to tell you why we're all screwed...

*points finger authoritatively
Comin' up!

 

[FGG]

This came up in my YouTube subscriptions today. It has optional captioning if you don't want audio. As far as I can tell, it's pretty accurate. This is what a more mainstream audience would probably be viewing to keep up with info on hearing loss developments; feel free to point out any inaccuracies you may spot. I didn't notice any.

Thanks for posting this! This is the only audiologist I have ever seen bother to explain to the public that audiograms only measure OHCs and word scores measure IHCs better (he left out that you have to lose a lot of them before it shows up on testing though).

 

[Diesel]

Thanks for posting this! This is the only audiologist I have ever seen bother to explain to the public that audiograms only measure OHCs and word scores measure IHCs better (he left out that you have to lose a lot of them before it shows up on testing though).

BUT MEH AUDIOGRAMS!

 

[Lucifer]

Thanks for posting this! This is the only audiologist I have ever seen bother to explain to the public that audiograms only measure OHCs and word scores measure IHCs better (he left out that you have to lose a lot of them before it shows up on testing though).

I was completely shocked when he said the same thing you said about word scores measuring IHCs and audiograms measuring OHCs.

We still have no clue if OHCs regrow as well since the multiple dosing dampens the effect but from the Phase 1b trials it did show that word scores in noise did improve.

Are word scores in noise still IHCs or are they OHCs?

 

[Chinmoku]

This came up in my YouTube subscriptions today. It has optional captioning if you don't want audio. As far as I can tell, it's pretty accurate. This is what a more mainstream audience would probably be viewing to keep up with info on hearing loss developments; feel free to point out any inaccuracies you may spot. I didn't notice any.

Seems pretty accurate to me and a good summary of what happened and what we may expect.

 

[Zugzug]

This came up in my YouTube subscriptions today. It has optional captioning if you don't want audio. As far as I can tell, it's pretty accurate. This is what a more mainstream audience would probably be viewing to keep up with info on hearing loss developments; feel free to point out any inaccuracies you may spot. I didn't notice any.

Haha, wow. That guy validated pretty much everything we've been saying: true failure from unclear reasons, but we shouldn't necessarily see previous word score improvements as a hoax.

I'm starting to wonder if @FGG is secretly that dude. He literally totally agrees with her lol.

 

[FGG]

In this video, I'm going to tell you why we're all screwed...

*points finger authoritatively
Comin' up!

Did you watch it? He didn't say that at all though...

He basically said what @Diesel and I have been saying which is that it looks like it may prefer IHCs. But this doesn't even mean it can't treat OHCs with multiple injections (but clearly not in rapid succession).

 

[FGG]

Haha, wow. That guy validated pretty much everything we've been saying: true failure from unclear reasons, but we shouldn't necessarily see previous word score improvements as a hoax.

I'm starting to wonder if @FGG is secretly that dude. He literally totally agrees with her lol.

He's me without the wig.

 

[serendipity1996]

Did you watch it? He didn't say that at all though...

He basically said what @Diesel and I have been saying which is that it looks like it may prefer IHCs. But this doesn't even mean it can't treat OHCs with multiple injections (but clearly not in rapid succession).

I was just skimming through the press release and noticed that in the final section entitled forward-looking statements, they mentioned "...including advancing FX-322 as a single-dose regimen and re-treatment at longer intervals..." I wonder if in future they would like to multi-dosing but more spaced out, as we have been speculating.

 

[Zugzug]

He's me without the wig.

Bobb is still doing victory laps. Maybe when he loops back around, you and @Diesel can join him and finish with a beer.

 

[Lucifer]

Does the improvement in word scores in noise in Phase 1b show that the OHCs did regrow?

 

[Guywithapug]

Did you watch it? He didn't say that at all though...

He basically said what @Diesel and I have been saying which is that it looks like it may prefer IHCs. But this doesn't even mean it can't treat OHCs with multiple injections (but clearly not in rapid succession).

No I didn't watch it yet, just some humor for the day I do enjoy his videos though.

 

[Tezcatlipoca]

Tl;dr: Plan to continue with FX-322 with single dosing only (and a better trial design), the results of the severe group and age-related group will help determine patient selection for that trial, they are very well funded for continuing.

So this is them committing to get the drug to market?

 

[Keith Handy]

Would you say it's a subjective test?

Hm, maybe to a degree. I could imagine, for example, someone having a very different regional accent from the recorded voice, and that throwing some of their words due to vowel shift.

 

[Gb3]

When one takes the WR test or SIN test, is it acceptable to say "I don't know"?

I was told to guess, but on some I had no idea.

 

[Tezcatlipoca]

I was told to guess, but on some I had no idea.

Same on my audiogram. The only scientific test I know where "guess" is involved, if audiograms can be considered scientific.

 

[FGG]

Does the improvement in word scores in noise in Phase 1b show that the OHCs did regrow?

Word scores don't assess OHCs well. Audiograms measure OHCs, which are also the hair cell type that hearing aids are a surrogate for. Which is why it's the testing standard.

OHC regrowth, if it occurs on first pass, is obviously minor by comparison (but rapid multi dosing is reportedly detrimental so we don't have good data on the full potential at this point).

My take is that to optimize any potential for OHC growth with a drug with a clear IHC preference (preference or need for IHC signaling), you'd have to treat the IHCs first (so multi dosing but with a bigger interval). Only then we would know how much OHC loss it could treat.

 

[FGG]

So this is them committing to get the drug to market?

Yes, they have not abandoned the drug and still see potential.

 

[Diesel]

Did you watch it? He didn't say that at all though...

He basically said what @Diesel and I have been saying which is that it looks like it may prefer IHCs. But this doesn't even mean it can't treat OHCs with multiple injections (but clearly not in rapid succession).

Doesn't that just make us worse, because an audiologist just confirmed what we've been writing, and audiologists are apparently the worst! Which makes us equally the worst!

 

[FGG]

BUT MEH AUDIOGRAMS!

Lol. Just reflecting on the fact that we were basically called Scientologists for suggesting what Dr. Cliff just did.

 

[Lucifer]

Same on my audiogram. The only scientific test I know where "guess" is involved, if audiograms can be considered scientific.

This is why I'm leaning that I have an OHC problem. I have no trouble with word scores so that rules out IHC. I do have trouble with words in noise so maybe that's an IHC problem but my audiograms look normal so most likely OHC problem.

Since I also suffer from tinnitus, it made it hard to distinguish whether it was my tinnitus or the beep in the audiogram.

 

[Keith Handy]

Doesn't that just make us worse, because an audiologist just confirmed what we've been writing, and audiologists are apparently the worst! Which makes us equally the worst!

You're not allowed to agree with an audiologist! Not even one! Cred rescinded!!

 

[FGG]

This is why I'm leaning that I have an OHC problem. I have no trouble with word scores so that rules out IHC. I do have trouble with words in noise so maybe that's an IHC problem but my audiograms look normal so most likely OHC problem.

Since I also suffer from tinnitus, it made it hard to distinguish whether it was my tinnitus or the beep in the audiogram.

You only have word score troubles when you lose a lot of IHCs.

This is why I think they were inadvertently selecting for "the unconscious biasers". Because you need people not in the severe range on audiogram (OHCs) but who happen to have lost a lot of IHCs. That's not usually how it works naturally...

Words in noise is very correlated to synaptopathy btw, which is separate from IHC loss and OHC loss.

 

[serendipity1996]

This is why I'm leaning that I have an OHC problem. I have no trouble with word scores so that rules out IHC. I do have trouble with words in noise so maybe that's an IHC problem but my audiograms look normal so most likely OHC problem.

Since I also suffer from tinnitus, it made it hard to distinguish whether it was my tinnitus or the beep in the audiogram.

You could also have synaptopathy if you struggle a lot with speech in noise issues.

 

[Tezcatlipoca]

Lol. Just reflecting on the fact that we were basically called Scientologists for suggesting what Dr. Cliff just did.

Lol they said it was a reach and conjecture, a "desperate rationalization". I always believed in you.

 

[Auricle]

I see. I wonder if it could be agitated further down using existing structures and white noise audio with a high pass filter. Sweep the filter down, letting in more low frequencies over time and let FX-322 ride the wave, like a surfer. Maybe bone conduction audio would work better for this method?

This looks similar to what you are suggesting:

Steady streaming as a method for drug delivery to the inner ear

There's also cochlear pumping, which looks more promising to me in the mechanical category:

Local Drug Delivery to the Entire Cochlea without Breaching Its Boundaries

 

[Zugzug]

Doesn't that just make us worse, because an audiologist just confirmed what we've been writing, and audiologists are apparently the worst! Which makes us equally the worst!

You're not understanding how this works. If Phase 2a was a success, the doubters knew all along. If it was a failure, it's all your fault. If Phase 2a results were a slam dunk, it overrides Phase 1. Since it's not, Phase 1 is the real efficacy test. If an audiologist agrees with you, it means you're right. If they disagree with you, it's because they are trying to sabotage the regeneration medicine industry.

If it turns out all of the 3 super responders were legit, I'm going to pretend like I never questioned how it happened. If the second Phase 2 is successful, I'm going to say that I was intentionally a bear to challenge our beliefs -- please thank me. If it's a failure, I'm going to say that I was so smart.

Any placebo patients that improve are diabolic lunatics, plotting to destroy the operation. Any FX-322 patients that improve are choir boys, have never uttered a swear word before, and gleefully showed off their improved hearing signal that was cleaner than a baby's bottom.

If someone's tinnitus got better, it was from the drug, but if it got worse, it was from the evil clinician who injured their middle ear.

If people enjoy this post, it's because I'm clever. If not, it's because I wasn't being serious.

 

[FGG]

Lol they said it was a reach and conjecture, a "desperate rationalization". I always believed in you.

I mean I'm not always right but I have reasons for my opinions that aren't based on a Ouija Board and my mood anyway...